Catalysis of guanine nucleotide exchange on eIF-2 by eIF-2B: is it a sequential or substituted enzyme mechanism?

The mechanism of action of the eukaryotic initiation factor eIF-2B in catalyzing the exchange of guanine nucleotides bound to eIF-2 is uncertain--evidence having been adduced for a sequential mechanism and for a substituted enzyme mechanism. Data purporting to support a substituted enzyme mechanism have been analysed and shown to be ambiguous and equally consistent with a sequential mechanism. Suitable rate constants for a sequential mechanism involving the transient formation of the quaternary complex eIF-2.eIF-2B.GDP.GTP are suggested.